Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient

Abstract

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

Figure 1

Renal biopsy demonstrating acute interstitial nephritis (H&E staining): there is edema and an extensive dense interstitial chronic inflammatory infiltrate in the cortex and medulla. (a) In the lower power photomicrograph (left, 100x), the renal cortex shows extensive interstitial chronic inflammation with occasional lymphocytic tubulitis (arrow). In areas of inflammation, there is evidence of acute tubular injury with proximal tubules demonstrating lumenal distension with epithelial flattening. There was no evidence of glomerulitis, vasculitis, or thrombotic microangiopathy. (b) The higher magnification photomicrograph (right, 600x) shows that the interstitial inflammatory cells comprised frequent eosinophils (arrows) as well as lymphocytes and fewer plasma cells.

Figure 2

Timeline showing the temporal relationship between the start of sunitinib and the rise of creatinine. Note the normal creatinine at baseline and the decrease of creatinine with steroids and hemodialysis.